DAVINCY trial: optimal Duration of (fos)Aprepitant prophylaxis for nausea and Vomiting INduced by ChemotherapY in children: a double-blind placebo-controlled crossover randomized phase III trial.

Other illness

• Only hemato-oncology patients on dexamethasone therapy and symptomatic primary or meta-static CNS malignancy patients causing nausea or vomiting are excluded from study participation.

• Age must be ≥ 6 months to ≤ 18 years at time of study entry.
• Patients do not receive scheduled blocks of chemotherapy containing corticosteroids as part of anti-tumour treatment during the study period.
• Patients aged greater than 16y with a Karnofsky score of 60 or more or patients aged 16y or less with a Lansky Play performance score of 60 or more.
• Patient must have a life expectancy of 3 months or more.
• Patients must not use antiemetic treatment within 48h before treatment (see appendix B).
• No use of CYP3A4 substrates/inhibitors within 7 days, or no CYP3A4 inducers within 30 days of treatment (see appendix B).
• Serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age.
• AST and ALT must be ≤ 5 x institutional ULN.
• Total bilirubin must be ≤ 1.5 x institutional ULN
• No history of QT prolongation.
• Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
• Patients must not receive radiation therapy to the abdomen or pelvis in the week before treatment.
• Female patients with infants must agree not to breastfeed their infants while on this study.
• Male and female patients of child-bearing potential must agree to use a highly effective method of contraception approved by the investigator during the study, following the CTFG recommendations.
• Patients have no history of prior grade 3/4 allergic reaction to any of the study drugs.
• Patients have no underlying gastrointestinal disease that may interfere with the absorption of the medication.
• Patient must not use benzodiazepines or opioids initiated within 48h before treatment, except for single doses of triazolam, temazepam, or midazolam.
• Continuation of chronic benzodiazepine or opioid therapy is permitted provided it was initiated ≥48 hours prior to study drug administration.
• In patients on chronic warfarin, acenocoumarol, tolbutamide or phenytoin (metabolised by CYP2C9) therapy should be monitored closely during treatment with (fos)aprepitant and for 14 days following each course of (fos)aprepitant.
• A documented malignancy.
• Patients need to receive moderate or highly emetogenic chemotherapy blocks, or chemotherapy not previously tolerated due to vomiting, for a minimum duration of 4 days.
• Chemotherapy schedules need to contain two similar courses of chemotherapy, which do not necessarily have to be consecutive courses.
• No symptomatic primary or metastatic CNS malignancy causing nausea or vomiting.